Post-transplant bone marrow aplasia is a major cause of morbidity and mortality after bone marrow transplant (BMT). Enhancing proliferation of short-term repopulating progenitors is an attractive strategy to accelerate post-transplant hematopoietic recovery, since the early reconstituting ability of these cells appears to be superior to that of long-term HCSs (LT-HSC). However, previously characterized extrinsic molecular pathways governing kinetics of short-term repopulating cells are also known to control LT-HSCs, raising a concern that manipulating those pathways in the transplant setting may lead to LT-HSC exhaustion.
Hematopoietic system is hierarchically organized and consists of 3 main compartments—slow dividing long-term stem cells, very rapidly dividing progenitors and non-dividing mature cells (the “effector” compartment)—all of which have distinct cell-surface marker profile. Stem cells support hematopoiesis throughout life-time, while progenitors have a capacity for massive short-term expansion in response to environmental stimuli such as infection or stress in order to generate a large number of mature blood cells. Long-term stem cells are absolutely required and sufficient for hematopoietic reconstitution following myeloablation. However, they are not as efficient at giving rise to mature cells as compared to more differentiating progenitors (Yang et al. Blood. 2005; 105:2717-2723). Cord blood, mobilized peripheral blood stem cells and bone marrow are currently used as a source of long-term hematopoietic stem cells in clinical bone marrow transplantation. All these products contain, together with stem cells, a variable proportion of hematopoietic progenitors.